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Hepatitis B virus upregulates host expression of α-1,2-mannosidases via the PPARα pathway

AIM: To assess the effects of hepatitis B virus (HBV) on the expression of host α-1,2-mannosidases and determine the underlying mechanisms. METHODS: We measured the expression levels of MAN1A1, MAN1A2, MAN1B1, and MAN1C1 in cell lines HepG2.2.15, HepN10, HepAD38 and HepG2 by Western blot. Viral anti...

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Autores principales: Hu, Song, Jiang, Li-Bin, Zou, Xiao-Jing, Yi, Wei, Tian, De-Ying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Baishideng Publishing Group Inc 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5116597/
https://www.ncbi.nlm.nih.gov/pubmed/27920474
http://dx.doi.org/10.3748/wjg.v22.i43.9534
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author Hu, Song
Jiang, Li-Bin
Zou, Xiao-Jing
Yi, Wei
Tian, De-Ying
author_facet Hu, Song
Jiang, Li-Bin
Zou, Xiao-Jing
Yi, Wei
Tian, De-Ying
author_sort Hu, Song
collection PubMed
description AIM: To assess the effects of hepatitis B virus (HBV) on the expression of host α-1,2-mannosidases and determine the underlying mechanisms. METHODS: We measured the expression levels of MAN1A1, MAN1A2, MAN1B1, and MAN1C1 in cell lines HepG2.2.15, HepN10, HepAD38 and HepG2 by Western blot. Viral antigens (HBsAg and HBeAg) in the culture medium were measured using the chemiluminescence method. HBV DNA quantification assays were performed using a commercial real-time PCR kit. Protein levels of human liver tissue α-1,2-mannosidases were also evaluated by Western blot. Plasmids containing seven individual viral genes of HBV (PTT22-HBx, PTT22-HBs, PTT22-preS2, PTT22-preS1, PTT22-HBc, PTT22-HBe, and PTT22-HBp) or control plasmids (PTT22-vector) were transfected into HepG2 cells. MK886 (PPARα) and GW9662 (PPARγ) inhibitors were used to explore the effects of HBV on α-1,2-mannosidase expression after the PPARα and PPARγ pathways were blocked. RESULTS: We showed that the expression of α-1,2-mannosidases was higher in stably transfected HBV cells than in controls. The expression levels of α-1,2-mannosidase were higher in AD38 cells than those in ND10 cells, which were in turn greater than those in G2.2.15 cells, and positively correlated with the expression of HBsAg in all the cell lines. Levels of α-1,2-mannosidase in non-tumorous liver tissues of HBV-related HCC patients were also higher than in the tissues from non-HBV-related HCC patients. Moreover, transfecting HepG2 cells with a component of the HBV viral envelope also increased the expression of α-1,2-mannosidases. However, this envelope protein component could not induce MAN1C1 expression in the presence of a PPARα inhibitor, MK886. We also found that MK886 did not affect the expression of MAN1C1 in AD38 cells without tetracycline in the culture medium. This phenomenon was not observed in the case of GW9662. CONCLUSION: Our results indicate that HBV increases the expression of α-mannosidases both in vitro and in vivo via activation of the PPARα pathway by its envelope protein.
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spelling pubmed-51165972016-12-05 Hepatitis B virus upregulates host expression of α-1,2-mannosidases via the PPARα pathway Hu, Song Jiang, Li-Bin Zou, Xiao-Jing Yi, Wei Tian, De-Ying World J Gastroenterol Basic Study AIM: To assess the effects of hepatitis B virus (HBV) on the expression of host α-1,2-mannosidases and determine the underlying mechanisms. METHODS: We measured the expression levels of MAN1A1, MAN1A2, MAN1B1, and MAN1C1 in cell lines HepG2.2.15, HepN10, HepAD38 and HepG2 by Western blot. Viral antigens (HBsAg and HBeAg) in the culture medium were measured using the chemiluminescence method. HBV DNA quantification assays were performed using a commercial real-time PCR kit. Protein levels of human liver tissue α-1,2-mannosidases were also evaluated by Western blot. Plasmids containing seven individual viral genes of HBV (PTT22-HBx, PTT22-HBs, PTT22-preS2, PTT22-preS1, PTT22-HBc, PTT22-HBe, and PTT22-HBp) or control plasmids (PTT22-vector) were transfected into HepG2 cells. MK886 (PPARα) and GW9662 (PPARγ) inhibitors were used to explore the effects of HBV on α-1,2-mannosidase expression after the PPARα and PPARγ pathways were blocked. RESULTS: We showed that the expression of α-1,2-mannosidases was higher in stably transfected HBV cells than in controls. The expression levels of α-1,2-mannosidase were higher in AD38 cells than those in ND10 cells, which were in turn greater than those in G2.2.15 cells, and positively correlated with the expression of HBsAg in all the cell lines. Levels of α-1,2-mannosidase in non-tumorous liver tissues of HBV-related HCC patients were also higher than in the tissues from non-HBV-related HCC patients. Moreover, transfecting HepG2 cells with a component of the HBV viral envelope also increased the expression of α-1,2-mannosidases. However, this envelope protein component could not induce MAN1C1 expression in the presence of a PPARα inhibitor, MK886. We also found that MK886 did not affect the expression of MAN1C1 in AD38 cells without tetracycline in the culture medium. This phenomenon was not observed in the case of GW9662. CONCLUSION: Our results indicate that HBV increases the expression of α-mannosidases both in vitro and in vivo via activation of the PPARα pathway by its envelope protein. Baishideng Publishing Group Inc 2016-11-21 2016-11-21 /pmc/articles/PMC5116597/ /pubmed/27920474 http://dx.doi.org/10.3748/wjg.v22.i43.9534 Text en ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved. http://creativecommons.org/licenses/by-nc/4.0/ This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.
spellingShingle Basic Study
Hu, Song
Jiang, Li-Bin
Zou, Xiao-Jing
Yi, Wei
Tian, De-Ying
Hepatitis B virus upregulates host expression of α-1,2-mannosidases via the PPARα pathway
title Hepatitis B virus upregulates host expression of α-1,2-mannosidases via the PPARα pathway
title_full Hepatitis B virus upregulates host expression of α-1,2-mannosidases via the PPARα pathway
title_fullStr Hepatitis B virus upregulates host expression of α-1,2-mannosidases via the PPARα pathway
title_full_unstemmed Hepatitis B virus upregulates host expression of α-1,2-mannosidases via the PPARα pathway
title_short Hepatitis B virus upregulates host expression of α-1,2-mannosidases via the PPARα pathway
title_sort hepatitis b virus upregulates host expression of α-1,2-mannosidases via the pparα pathway
topic Basic Study
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5116597/
https://www.ncbi.nlm.nih.gov/pubmed/27920474
http://dx.doi.org/10.3748/wjg.v22.i43.9534
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